Arginase I Attenuates Inflammatory Cytokine Secretion Induced by Lipopolysaccharide in Vascular Smooth Muscle Cells

Abstract

Objective-Inflammation plays an important role in atherosclerosis. Arginase I (Arg I) promotes the proliferation of vascular smooth muscle cells; however, the effect of Arg I on inflammation remains unknown. The present study investigated the role of Arg I in inflammation in vitro and in vivo. Methods and Results-Quantitative reverse transcription-polymerase chain reaction and Western blot analysis demonstrated that Arg I inhibited tumor necrosis factor-␣ production induced by lipopolysaccharide in human aortic smooth muscle cells. Inducible nitric oxide synthase substrate competition and nuclear factor-B activation were main contributors to lipopolysaccharide-mediated inflammatory cytokine generation. However, Arg I could attenuate the function of inducible nitric oxide synthase and inhibit the subsequent nuclear factor-B activation, leading to inhibition of tumor necrosis factor-␣ generation. Furthermore, upregulation of Arg I significantly decreased macrophage infiltration and inflammation in atherosclerotic plaque of rabbits, whereas downregulation of Arg I aggravated these adverse effects. Conclusion-The

Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease

“…5 Previous studies have shown that Arginase1 can serve as an unexpected beneficial role of Arginase1 in inflammatory diseases such as atherosclerosis. 36 However, the anti-inflammatory effect of Arginase1 in the CNS has not been reported. We demonstrate that the suppression of either Jmjd3 or Arginase1 can enhance NO production in a similar manner; however, introduction of full-length Arginase1 into Jmjd3-knockdown cells could suppress the NO elevation and attenuate neuron death.…”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…In patients with advanced atheroma, this might have a destabilizing impact on plaque, inasmuch as increased expression of arginase I is reported to have a stabilizing impact in that regard (Wang et al 2014;Teupser et al 2006;Wang et al 2011). Conceivably, this might help to explain why a controlled trial of arginine supplementation (9 g daily) large and long enough (6 months) to report hard endpoints, enrolling patients who had recently suffered a myocardial infarct, observed six deaths in the treatment group, versus zero in those receiving placebo (P = 0.01); as a result, the trial was terminated sooner than planned (Boger 2008;Schulman et al 2006).…”

Binding of EBP50 to Nox organizing subunit p47 phox is pivotal to cellular reactive species generation and altered vascular phenotype

“…Ex vivo EPR studies on aortic rings also showed absence of an O 2 •-signal in response to AngII in EBP50 KO, correlating with findings in Nox1 KO. Moreover, in vivo data demonstrated that in response to another robust inducer of Nox-derived ROS, LPS (27)(28)(29)(30)(31)(32)(33), vascular medial smooth muscle oxidation was absent in EBP50 KO mice. Because Nox1 is a major source of O 2…”

“…Mice were subjected to vehicle or lipopolysaccharide (LPS) (10 mg·kg −1 , i.p. ; 16 h), another well-established activator of ROS and Nox activity (27)(28)(29), including Nox1 (30-33), the major Nox in the media of conduit arteries (1,2,22). Femoral arteries from these mice were isolated, sectioned, and stained for 4-hydroxynonenal (4-HNE, a footprint marker of lipid oxidation and oxidative stress).…”